A new clinical practice update released by AGA and published in Gastroenterology shares the foundation of hepatocellular carcinoma (HCC) surveillance remains semiannual ultrasound plus alpha-fetoprotein (AFP), even as blood-based biomarkers, abbreviated MRI, and risk-based surveillance strategies are being evaluated for clinical use.
The expert review was led by Nicole E. Rich, MD, of the Division of Digestive and Liver Diseases at UT Southwestern Medical Center, with coauthors Augusto Villanueva, MD, PhD, Jorge A. Marrero, MD, and Fasiha Kanwal, MD, MSHS.
The review spans the full HCC surveillance pathway, beginning with an emphasis that the most effective strategy for reducing HCC morbidity and mortality is preventing cirrhosis. This includes addressing chronic viral hepatitis through vaccination and treatment, recognizing and treating alcohol use disorder, and managing metabolic risk factors and chronic liver disease earlier in their course.
Although viral hepatitis remains important, growing numbers of cases are tied to metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease. At the same time, surveillance remains underused, and many tumors are still diagnosed too late for curative treatment.
The update emphasizes that standard surveillance has not changed. The preferred strategy remains ultrasound plus AFP every six months in patients at sufficient risk, particularly those with cirrhosis of any etiology and selected patients with chronic hepatitis B virus (HBV) infection without cirrhosis. This approach improves early-stage detection, expands access to curative therapy, and is associated with improved early detection and survival compared with annual surveillance.
The update also clarifies where surveillance is not recommended. Among patients without cirrhosis, only a subset of those with chronic HBV infection should undergo routine surveillance. For patients without cirrhosis from other etiologies, including most with MASLD or cured hepatitis C, HCC incidence remains too low to justify surveillance. The authors leave room for individualized discussion when fibrosis staging is uncertain or when additional risk factors, such as family history, complicate the picture.
Another key component of the update is consideration of the downsides of surveillance. Although ultrasound and AFP are noninvasive, false-positive results can trigger additional imaging, biopsy, patient anxiety, missed work, and financial burden. Surveillance is beneficial but is associated with potential harms, and it should be pursued in patients who are well enough to benefit from early cancer detection and possible treatment. In patients with limited life expectancy or those who are not candidates for liver transplantation or HCC-directed therapy, the balance may shift away from routine surveillance.
The update describes biomarkers as promising; however, current evidence does not support their routine use. Novel blood-based biomarkers, including GALAD and other composite panels, are described as promising but are not recommended for routine surveillance. Some are already commercially available, yet the evidence remains insufficient for them to replace or routinely augment guideline-based surveillance in everyday practice. Janice Jou, MD, MHS, Professor of Medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland, and an associate editor of GI & Hepatology News, said the imperfection of current tests is itself a talking point for clinicians. "One strategy to address this uncertainty in practice is to discuss it with the patient directly," Dr. Jou said. She also noted that the moment can be reframed as an opportunity: "This is also an opportunity to discuss opportunities for our patients to participate in clinical trials to better our understanding of which HCC surveillance strategies are most effective."
Similarly, multicancer early-detection blood tests are not recommended for HCC surveillance. Abbreviated MRI is also described as promising, but is not currently recommended for routine use in place of standard surveillance. Ongoing trials, including TRACER and PREMIUM, are expected to clarify whether biomarker-based and MRI-based approaches can improve outcomes enough to change practice.
The review also addresses the need for better risk stratification. Many HCC risk scores have been developed for patients with cirrhosis, but few have undergone enough validation to support routine use in clinical practice. Risk stratification for cirrhosis remains an active area of development, but current models should not yet be used to routinely determine who should or should not undergo surveillance.
There is one important exception. In patients with chronic HBV infection without cirrhosis, the authors note that PAGE-B and REAL-B scores can help stratify future HCC risk and may be useful in guiding surveillance decisions. These tools are intended to support, but not replace, clinical judgment.
For practicing gastroenterologists and hepatologists, the message is both practical and cautionary: prevent cirrhosis when possible, use ultrasound plus AFP consistently in appropriate patients, avoid overextending surveillance into low-risk groups, and resist adopting emerging tests before the evidence is available. Emerging approaches remain under investigation, and current standard surveillance should be maintained. Dr. Jou pointed to under-surveillance, not over-surveillance, as the more pressing gap in everyday practice. "With the high burden of patients who are at risk for HCC and the diminishing hepatology workforce to care for liver disease patients, inconsistent surveillance in patients who need it is likely to be a significant ongoing issue," she said.
A majority of HCC is still diagnosed either incidentally or when patients present with symptoms, she noted, adding that identifying at-risk patients and operationalizing recall systems requires infrastructure and funding that many practices lack. "These and other factors affecting the HCC care continuum remain significant barriers to the effectiveness of HCC surveillance," Dr. Jou said.
Authors reported multiple industry relationships, including consulting and advisory roles with several pharmaceutical companies and research support from the NIH. One author also holds stock options and is listed on a related patent. Other authors reported no conflicts.